Billions of neurons (nerve cells) in the human brain are wired together in an intricate network that communicates through electrical pulses and chemical signals. Despite making progress in understanding some of the brain functions, such as those regulating sleep, storing memories, and making decisions, neuroscientists are unable to visualize the entire ‘wiring diagram’ of neural connections within the brain, using techniques currently available.

Now, for the first time, researchers at California Institute of Technology (Caltech) in the US have been able to easily see neural connections and the flow of communications in real time in the brain of live house flies. The new technique has the potential to help scientists understand neural circuits within human brains.

When two neurons connect, they link together with a structure called a synapse, a space through which one neuron can send and receive electrical and chemical signals to or from another neuron. Even if multiple neurons are very close together, they need synapses to truly communicate.

Researchers at Caltech developed a technique, called Trans-neuronal Control of Transcription (TRACT) to trace the flow of information across synapses. Using genetically engineered Drosophila fruit flies, TRACT allows researchers to observe which neurons are ‘talking’ and which neurons are ‘listening’ by prompting the connected neurons to produce glowing proteins.

With TRACT, when a neuron ‘talks’ — transmits a chemical or electrical signal across a synapse — it will also produce and send along a fluorescent protein that lights up both the talking neuron and its synapses with a particular color. Any neurons ‘listening’ to the signal receive this protein, which binds to a so-called receptor molecule, which was genetically built-in by the researchers, on the receiving neuron's surface. The binding of the signal protein activates the receptor and triggers the neuron it is attached to in order to produce its own, differently colored fluorescent protein. In this way, communication between neurons becomes visible. Using a type of microscope that can peer through a thin window installed on the fly's head, the researchers could observe the colorful glow of neural connections in real time as the fly grew, moved and experienced changes in its environment.

Many neurological and psychiatric conditions, such as autism and schizophrenia, are thought to be caused by altered connections between neurons. Using TRACT, scientists can monitor the neuronal connections in the brains of hundreds of flies each day, allowing them to make comparisons at different stages of development, between the sexes, and in flies that have genetic mutations. Thus, TRACT could be used to determine how different diseases perturb the connections within brain circuits. Additionally, because neural synapses change over time, TRACT allows the monitoring of synapse formation and destruction from day to day. Being able to see how and when neurons form or break synapses will be critical to understanding how the circuits in the brain assemble as the animal grows, and how they fall apart with age or disease.

TRACT is seen as a new tool that will allow scientists to create wiring diagrams of brains and determine the function of connected neurons. This information could in the future provide important clues towards understanding the complex workings of the human brain and its diseases.